Although tribes differ with regard to the use of alcohol Native Americans, as a group, have the highest alcohol-related death rates of all ethnic groups in the United States. However, how and why alcoholism is more prevalent in some Native American communities remains unclear The overall objective of this research plan is to enhance understanding of the biological risk and protective factors related to alcohol dependence and alcohol-related problems in reservation dwelling Indians indigenous to San Diego county (collectively called Mission Indians). The studies proposed in this application include cross-sectional studies in Mission Indian adults and adolescents, as well as longitudinal studies in Native American children and adolescents. This design allows for the investigation of specific genetic and environmental risk factors existing both prior to alcohol exposure and during the development of drinking patterns. The four aims of the study are: (1) To find identifiable neurobiological factors in Native American youth who progress from alcohol use to abuse, and to dependence; (2) To document whether exposure to high levels of alcohol in adolescence lead to specific and detrimental medical and psychological outcomes; (3) To identify circumstances and mechanisms of behavioral change that lead to either continued alcohol use and disability or remission from alcoholism in this population; and (4) To determine why Native American Mission Indian adults are at such high risk for alcoholism through the identification of specific genetic and environmental factors. These studies have the potential to verify whether Native Americans have any specific biological/genetic, psychosocial or behavioral factors that may help to explain the high risk for alcoholism within the tribes evaluated. The identification of such variables may potentially be useful in the development of specific prevention and treatment programs for this population as well as other Native American tribes.